The goals of this project are to determine the structure and function of the nuclear lamins. The lamins are Type V intermediate filament proteins that are found in the nuclear lamina and in the nucleoplasm. Mutations in the nuclear lamins have been linked to many human diseases including different forms of muscular dystrophy, cardiomyopathies and premature aging. The specific aims of this grant are targeted towards a greater understanding of the function of the lamins in DNA replication, transcription, nuclear assembly and disassembly, and in the overall molecular architecture of the nucleus. Structural studies will be undertaken at both the light and electron microscope levels of resolution. Live cell imaging will also be used employing the jellyfish green fluorescent protein (GFP). Other methods will include the silencing of specific lamins using siRNA and a variety of biochemical and molecular methods aimed at determining the protein-protein interactions required for lamin assembly and structure. In addition, attempts will be made to identify the specific binding partners, which link the A and B-type lamins to the RNA polymerase II machinery and to the DNA replication elongation complex.